Abstract Developing new interventions that incorporate the "diverse needs and circumstances of people with mental illness," particularly in primary care and community settings, is a key NIMH strategic objective. Prevention of mental disorders has become a priority for the NIMH, which emphasizes the importance of developing "new and better interventions" to "...preempt the occurrence of disease." These interventions must (1) work in multiple and diverse settings (e.g. primary care);(2) be suitable for delivery outside of traditional mental health systems (3) use new technologies;(4) build on previous clinical trials;(5) reduce identified disorders/enhance functional outcomes;(6) include families and (7) be tailored to the individual. Despite these NIMH guidelines, while primary care physicians remain the first line providers for at-risk adolescents, there is no widely available, low cost and culturally acceptable preventive approach that targets depression in primary care settings. To address this gap and specified NIMH priority, Dr. Van Voorhees developed and conducted a phase 2 clinical trial of a primary care Internet-based depression prevention intervention (CATCH-IT, Competent Adulthood Transition with Cognitive Behavioral Humanistic and Interpersonal Training). In this study, the high intensity arm (i.e., motivational interview + internet site) demonstrated significant reductions in depressed mood and increases in protective factors (social support, motivation) and lower incidence of depressive episodes over 12 months (7% versus 28%), compared to the low intensity arm (internet site referral + only physician brief advice). We now propose the next step study, a phase 3 efficacy study. In this 4-year, two-site randomized clinical trial, we propose to test the efficacy of the CATCH-IT primary care/Internet based depression prevention intervention against treatment as usual (TAU) in preventing the onset of depressive episodes in an intermediate to high risk group of adolescents aged 13-18. We plan to (a) identify high risk adolescents based on elevated scores on the PHQ-A, a screening measure of depressive symptoms;(b) recruit 320 (160 per site) of these at-risk adolescents to be randomized into either the CATCH-IT or the TAU group;(c) assess outcomes at 2, 8, 12, 18, and 24 months post intake on measures of depressive symptoms, depressive diagnoses, other mental disorders, and on measures of role impairment in education, quality of life, attainment of educational milestones, and family functioning;and (d) conduct exploratory analyses to examine the effectiveness of this intervention program, moderators of protection, and potential ethnic and cultural differences in intervention response. This application builds on a K-08 funded research program (Van Voorhees) that has resulted in the development, preliminary testing, and revision of this intervention, which is now ready for an efficacy trial.